001 Spiritual Counseling Room Around40 Single Tomomi (Japanese Edition)

Different analytical methods such as oil spreading and surface activity measurements were utilized to screen the biosurfactant-producing bacteria isolated from the brine of a specific oil reservoir located in the southwest of Iran. The produced biosurfactant caused substantial surface tension reduction of the growth medium and interfacial tension reduction between oil and brine to 31 and 3. A novel set of core flooding tests, including in situ and ex situ scenarios, was designed to explore the potential of the isolated consortium as an agent for MEOR process.

Besides, the individual effects of wettability alteration and IFT reduction on oil recovery efficiency by this process were investigated. The results show that the wettability alteration of the reservoir rock toward neutrally wet condition in the course of the adsorption of bacteria cells and biofilm formation are the dominant mechanisms on the improvement of oil recovery efficiency. The relative abundance of predicted genes associated with ammonia-oxidation, nitrate reduction , and biomass decomposition in mineral soil are altered by intensive timber harvest.

Forest ecosystems in the southern United States are substantially altered by anthropogenic disturbances such as timber harvest and land conversion, with effects being observed in carbon and nutrient pools as well as biogeochemical processes. Furthermore, the desire to develop renewable energy sources in the form of biomass extraction from logging residues may result in alterations in soil community structure and function.

While the impact of forest management on soil physicochemical properties of the region has been studied, its' long-term effect on soil bacterial community composition and metagenomic potential is relatively unknown, especially at deeper soil depths. This study investigates how intensive organic matter removal intensities associated with timber harvest influence decadal-scale alterations in bacterial community structure and functional potential in the upper 1-m of the soil profile, 18 years post-harvest in a Pinus taeda L.

Amplicon sequencing of the 16S rRNA gene was used in conjunction with soil chemical analyses to evaluate treatment-induced differences in community composition and potential environmental drivers of associated change. Furthermore, functional potential was assessed by using amplicon data to make metagenomic predictions. Results indicate that increasing organic matter removal intensity leads to altered community composition and the relative abundance of dominant OTUs annotated to Burkholderia and Aciditerrimonas.

The relative abundance of predicted genes associated with dissimilatory nitrate reduction and denitrification were highest in the most intensively harvested treatment while genes involved in nitrification were significantly lower in the most intensively harvested treatment. Furthermore, genes associated with glycosyltransferases were significantly reduced with increasing harvest intensity while polysaccharide lyases increased. These results imply that intensive organic matter removal may create. Ethyl acetate fraction from methanol extraction of Vitis thunbergii var. It is traditionally used for the treatment of diarrhea, hypertension, neuroprotection, jaundice, and arthritis.

We used the wild-collected VTT and sterilized them to establish the plant tissue culture, and then took the leaves for DNA sequencing to determine its original base. We use methanol to extract VTT in four different solvents: These four preliminary extracts were used to treat human prostate cancer DU cells in vitro. We use the flow cytometry to check the cell survival situation. Finally, we found the ethyl acetate layer roughing product referred VTEA in human prostate cancer apoptotic effects of cell line DU In the present studies, we use the crude extract of VTT to examine whether or not it can induce apoptosis of DU cells in vitro.

Viability assays for extracts of VTT treatment showed that it had dose-dependent effect on human prostate cancer DU cells. We also found that the extract of VTT induces time-dependent mitochondrial and intrinsic-dependent apoptosis pathways. The in vitro cytotoxic effects were investigated by cell cycle analysis and the determination of apoptotic DNA fragmentation in DU cells. Finally, the expression of relevant proteins was analyzed by Western blot analysis.

These results promoted us to further evaluate apoptosis associated proteins and elucidate the possible signal pathway in DU cells after treated with the extract of VTT. Sulfide mineralogy and the contents and isotope compositions of sulfur were analyzed in a complete oceanic volcanic section from IODP Hole D in the eastern Pacific, in order to investigate the role of microbes and their effect on the sulfur budget in altered upper oceanic crust.

Basalts in the m thick volcanic section are affected by a pervasive low-temperature background alteration and have mean sulfur contents of ppm, reflecting loss of sulfur relative to fresh glass through degassing during eruption and alteration by seawater. Although sulfur was lost locally, sulfur was subsequently gained through fixation of seawater-derived sulfur in secondary pyrite and marcasite in veins and in concentrations at the boundary between alteration halos and host rocks. The bulk volcanic section may have gained or lost sulfur overall.

The annual flux of microbial sulfur into oceanic basement based on Hole D is XmolSyr-1, within an order of magnitude of the riverine sulfate source and the sedimentary pyrite sink. Results indicate a flux of bacterially derived sulfur that is fixed in upper ocean basement of X molcm-2yr-1 over 15m. This is comparable to that in open ocean sediment sites, but is one to two orders of magnitude less than for ocean margin sediments.

The global annual subduction of sulfur in altered oceanic basalt lavas based. Forest fuel reduction alters fire severity and long-term carbon storage in three Pacific Northwest ecosystems. Two forest management objectives being debated in the context of federally managed landscapes in the U. Pacific Northwest involve a perceived trade-off between fire restoration and carbon sequestration. The former strategy would reduce fuel and therefore C that has accumulated through a century of fire suppression and exclusion which has led to extreme fire risk in some areas.

The latter strategy would manage forests for enhanced C sequestration as a method of reducing atmospheric CO2 and associated threats from global climate change. We explored the trade-off between these two strategies by employing a forest ecosystem simulation model, STANDCARB, to examine the effects of fuel reduction on fire severity and the resulting long-term C dynamics among three Pacific Northwest ecosystems: Our simulations indicate that fuel reduction treatments in these ecosystems consistently reduced fire severity.

However, reducing the fraction by which C is lost in a wildfire requires the removal of a much greater amount of C, since most of the C stored in forest biomass stem wood, branches, coarse woody debris remains unconsumed even by high-severity wildfires. For this reason, all of the fuel reduction treatments simulated for the west Cascades and Coast Range ecosystems as well as most of the treatments simulated for the east Cascades resulted in a reduced mean stand C storage.

One suggested method of compensating for such losses in C storage is to utilize C harvested in fuel reduction treatments as biofuels. Our analysis indicates that this will not be an effective strategy in the west Cascades and Coast Range over the next years. We suggest that forest management plans aimed solely at ameliorating increases in atmospheric CO2 should forgo fuel reduction treatments in these ecosystems, with the possible exception of. Supramammillary serotonin reduction alters place learning and concomitant hippocampal, septal, and supramammillar theta activity in a Morris water maze.

Hippocampal theta activity is related to spatial information processing, and high-frequency theta activity, in particular, has been linked to efficient spatial memory performance. Theta activity is regulated by the synchronizing ascending system SAS , which includes mesencephalic and diencephalic relays. The supramamillary nucleus SUMn is located between the reticularis pontis oralis and the medial septum MS , in close relation with the posterior hypothalamic nucleus PHn , all of which are part of this ascending system. It has been proposed that the SUMn plays a role in the modulation of hippocampal theta-frequency; this could occur through direct connections between the SUMn and the hippocampus or through the influence of the SUMn on the MS.

Serotonergic raphe neurons prominently innervate the hippocampus and several components of the SAS, including the SUMn. Serotonin desynchronizes hippocampal theta activity, and it has been proposed that serotonin may regulate learning through the modulation of hippocampal synchrony. Because it has been reported that SUMn inactivation with lidocaine impairs the consolidation of reference memory, we asked whether changes in hippocampal theta activity related to learning would occur through serotonin depletion in the SUMn, together with deficiencies in memory.

The EEG power in each region and the coherence between the different regions were evaluated. Serotonin depletion in the SUMn induced deficient spatial learning and altered the expression of hippocampal high-frequency theta activity. These results provide evidence in. Genetic and chemical reductions in protein phosphatase activity alter auxin transport, gravity response, and lateral root growth. Auxin transport is required for important growth and developmental processes in plants, including gravity response and lateral root growth. Several lines of evidence suggest that reversible protein phosphorylation regulates auxin transport.

Arabidopsis rcn1 mutant seedlings exhibit reduced protein phosphatase 2A activity and defects in differential cell elongation. Here we report that reduced phosphatase activity alters auxin transport and dependent physiological processes in the seedling root. Root basipetal transport was increased in rcn1 or phosphatase inhibitor-treated seedlings but showed normal sensitivity to the auxin transport inhibitor naphthylphthalamic acid NPA.

Phosphatase inhibition reduced root gravity response and delayed the establishment of differential auxin-induced gene expression across a gravity-stimulated root tip. An NPA treatment that reduced basipetal transport in rcn1 and cantharidin-treated wild-type plants also restored a normal gravity response and asymmetric auxin-induced gene expression, indicating that increased basipetal auxin transport impedes gravitropism. In contrast to basipetal transport, root acropetal transport was normal in phosphatase-inhibited seedlings in the absence of NPA, although it showed reduced NPA sensitivity.

Lateral root growth also exhibited reduced NPA sensitivity in rcn1 seedlings, consistent with acropetal transport controlling lateral root growth. These results support the role of protein phosphorylation in regulating auxin transport and suggest that the acropetal and basipetal auxin transport streams are differentially regulated.

Long-term obesity promotes alterations in diastolic function induced by reduction of phospholamban phosphorylation at serine without affecting calcium handling. Morphological and histological analyses were assessed. Left ventricular cardiac function was assessed in vivo by echocardiographic evaluation and in vitro by papillary muscle.

Obesity promoted cardiac hypertrophy without alterations in interstitial collagen levels. Ob rats had increased endocardial and midwall fractional shortening, posterior wall shortening velocity, and A-wave compared with C rats. Cardiac index, early-to-late diastolic mitral inflow ratio, and isovolumetric relaxation time were lower in Ob than in C.

It has been linked to reductions in total brain volume and subcortical abnormalities. However, owing to heterogeneity within and between studies and limited sample sizes, findings on the neuroanatomical substrates of ADHD have shown considerable variability. To examine whether ADHD is linked to alterations in whole-brain and subcortical volumes and to study familial underpinnings of brain volumetric alterations in ADHD. In this cross-sectional study, we included participants from the large and carefully phenotyped Dutch NeuroIMAGE sample collected from September December consisting of participants with ADHD, of their unaffected siblings, and typically developing control individuals mean age, Whole-brain volumes total brain and gray and white matter volumes and volumes of subcortical regions nucleus accumbens, amygdala, caudate nucleus, globus pallidus, hippocampus, putamen, thalamus, and brainstem were derived from structural magnetic resonance imaging scans using automated tissue segmentation.

Regression analyses revealed that relative to control individuals, participants with ADHD had a 2. Unaffected siblings had total brain and total gray matter volumes intermediate to participants with ADHD and control individuals. Significant age-by-diagnosis interactions showed that older age was linked to smaller caudate P Aluminum oxide nanoparticles alter cell cycle progression through CCND1 and EGR1 gene expression in human mesenchymal stem cells.

Aluminum oxide nanoparticles Al2 O3 -NPs are important ceramic materials that have been used in a variety of commercial and industrial applications. However, the impact of acute and chronic exposure to Al2 O3 -NPs on the environment and on human health has not been well studied. Nuclear condensation and fragmentation, chromosomal DNA fragmentation, and cytoplasmic vacuolization were observed in Al2 O3 -NP-exposed cells.

The nuclear morphological changes indicated that Al2 O3 -NPs alter cell cycle progression and gene expression. Myg1-deficient mice display alterations in stress-induced responses and reduction of sex-dependent behavioural differences. Myg1 Melanocyte proliferating gene 1 is a highly conserved and ubiquitously expressed gene, which encodes a protein with mitochondrial and nuclear localization.

In the current study we demonstrate a gradual decline of Myg1 expression during the postnatal development of the mouse brain that suggests relevance for Myg1 in developmental processes. The main finding of the present study was that Myg1 invalidation decreases several behavioural differences between male and female animals that were obvious in wild-type mice, indicating that Myg1 contributes to the expression of sex-dependent behavioural differences in mice.

Taken together, we provide evidence for the involvement of Myg1 in anxiety- and stress-related responses and suggest that Myg1 contributes to the expression of sex-dependent behavioural differences. Sulfur geochemistry and microbial sulfate reduction during low-temperature alteration of uplifted lower oceanic crust: Sulfide petrography plus whole rock contents and isotope ratios of sulfur were measured in a 1.

Compared to fresh gabbro containing — ppm sulfur our data indicate an overall addition of sulfide to the lower crust. Depth trends in sulfide—sulfur contents and sulfide mineral assemblages indicate a late-stage downward penetration of seawater into the lower 1 km of Hole B. Our results show that under appropriate temperature conditions, a subsurface biosphere can persist in the lower oceanic crust and alter its geochemistry.

Energy output reduction and surface alteration of quartz and sapphire tips following Er: YAG laser contact irradiation for tooth enamel ablation. Despite the recent increase in application of Er: YAG laser for various dental treatments, limited information is available regarding the contact tips. This study examined the changes in energy output and surface condition of quartz and sapphire contact tips after Er: Ten sets of unused quartz or sapphire contact tips were employed for contact irradiation to sound enamel of extracted teeth. The teeth were irradiated with Er: The energy output was measured before and every 5 minutes after irradiation, and the changes in morphology and chemical composition of the contact surface were analyzed.

The energy output significantly decreased with time in both tips. The energy output from the sapphire tips was generally higher on average than that of the quartz. The contact surfaces of all the used quartz tips were concave and irregular. Most of the sapphire tips also appeared rough with crater formation and fractures, except for a few tips in which a high energy output and the original smooth surface were maintained. Spots of melted tooth substances were seen attached to the surface of both tips.

In contact enamel ablation, the sapphire tip appeared to be more resistant than the quartz tip. The quartz tips showed similar patterns of energy reduction and surface alteration , whereas the sapphire tips revealed a wider and more characteristic variation among tips. Altered cortisol metabolism in polycystic ovary syndrome: Increased peripheral metabolism of cortisol may occur by enhanced inactivation of cortisol by 5alpha-reductase 5alpha-R or impaired reactivation of cortisol from cortisone by 11beta-hydroxysteroid dehydrogenase type 1 11beta-HSD1 resulting in decreased negative feedback suppression of ACTH secretion maintaining normal plasma cortisol concentrations at the expense of androgen excess.

We have tested whether any enzyme dysregulation was related to circulating insulin or androgen concentrations in women with PCOS and have sought to clarify their relationship with obesity. First, to avoid obesity-related effects on cortisol metabolism, 18 lean women with PCOS were compared with 19 lean controls who were closely matched for body mass index BMI. Oncogene-induced DNA replication stress contributes critically to the genomic instability that is present in cancer.

However, elucidating how oncogenes deregulate DNA replication has been impeded by difficulty in mapping replication initiation sites on the human genome. Here, using a sensitive assay to monitor nascent DNA synthesis in early S phase, we identified thousands of replication initiation sites in cells before and after induction of the oncogenes CCNE1 and MYC. Remarkably, both oncogenes induced firing of a novel set of DNA replication origins that mapped within highly transcribed genes.

These ectopic origins were normally suppressed by transcription during G1, but precocious entry into S phase, before all genic regions had been transcribed, allowed firing of origins within genes in cells with activated oncogenes. Forks from oncogene-induced origins were prone to collapse, as a result of conflicts between replication and transcription, and were associated with DNA double-stranded break formation and chromosomal rearrangement breakpoints both in our experimental system and in a large cohort of human cancers.

Thus, firing of intragenic origins caused by premature S phase entry represents a mechanism of oncogene-induced DNA replication stress that is relevant for genomic instability in human cancer. These events include commitment in In particular, we do not know what substrates have to be The purpose of the present work is to develop. Catastrophic windstorm and fuel- reduction treatments alter ground beetle Coleoptera: Carabidae assemblages in a North American sub-boreal forest.

We studied the short-term effects of a catastrophic windstorm and subsequent salvage-logging and prescribed-burning fuel- reduction treatments on ground beetle Coleoptera: Carabidae assemblages in a sub-boreal forest in northeastern Minnesota, USA. Dose addition models based on biologically-relevant reductions in fetal testosterone accurately predict postnatal reproductive tract alterations by a phthalate mixture in rats. Challenges in cumulative risk assessment of anti-androgenic phthalate mixtures include a lack of data on all the individual phthalates and difficulty determining the biological relevance of reduction in fetal testosterone T on postnatal development.

The objectives of the curren How light-harvesting semiconductors can alter the bias of reversible electrocatalysts in favor of H2 production and CO2 reduction. The most efficient catalysts for solar fuel production should operate close to reversible potentials, yet possess a bias for the fuel-forming direction. This catalytic rectification effect can arise for a reversible electrocatalyst attached to a semiconductor electrode if the electrode transforms between semiconductor- and metallic-like behavior across the same narrow potential range reduction. The purpose of this study was to determine if ablation of the nuclear receptor, receptor-inactivating protein RIP , altered this response.

This occurred alongside increased hexokinase II HKII protein content in adipose tissue and skeletal muscle, but independent of changes in circulating insulin or indices of lipolysis. Hyaluronan HA , a large anionic polysaccharide glycosaminoglycan , is a major constituent of the extracellular matrix of the adult brain. To address its function, we examined the neurophysiology of knock-out mice deficient in hyaluronan synthase Has genes. Imaging of the diffusion of a fluorescent marker revealed that the transit of molecules through the ECS of this layer was reduced.

Our results provide the first direct evidence for the physiological role of HA in the regulation of ECS volume, and suggest that HA-based preservation of ECS volume may offer a novel avenue for development of antiepileptogenic treatments. Karyotype evolution in Phalaris Poaceae: The role of reductional dysploidy, polyploidy and chromosome alteration in a wide-spread and diverse genus. Karyotype characteristics can provide valuable information on genome evolution and speciation, in particular in taxa with varying basic chromosome numbers and ploidy levels.

Due to its worldwide distribution, remarkable variability in morphological traits and the fact that ploidy change plays a key role in its evolution, the canary grass genus Phalaris Poaceae is an excellent study system to investigate the role of chromosomal changes in species diversification and expansion. To identify distinct karyotype structures and to trace chromosome evolution within the genus, we apply fluorescence in situ hybridisation FISH of 5S and 45S rDNA probes in four diploid and four tetraploid Phalaris species of both basic numbers.

We recognize three different genomes in the genus: Both auto- and allopolyploidy of genomes B and C are suggested for the formation of tetraploids. The chromosomal divergence observed in Phalaris can be explained by the occurrence of dysploidy, the emergence of three different genomes, and the chromosome rearrangements accompanied by karyotype change and polyploidization. Putnam's criticisms of the identity theory attack a straw man. Fodor's criticisms of reduction attack a straw man. Properly interpreted, Nagel offered a conception of reduction that captures everything a physicalist could want.

I update Nagel, introducing the idea of overlap, and show why multiple realization poses no challenge to reduction so construed. Melanogenesis stimulation in BF10 melanoma cells induces cell cycle alterations , increased ROS levels and a differential expression of proteins as revealed by proteomic analysis. Considering that stimulation of melanogenesis may lead to alterations of cellular responses, besides melanin production, our main goal was to study the cellular effects of melanogenesis stimulation of BF10 melanoma cells.

Our results show increased levels of the reactive oxygen species after 15 h of melanogenesis stimulation. Following 48 h of melanogenesis stimulation, proliferation was inhibited by induction of cell cycle arrest in the G 1 phase and the expression levels of p21 mRNA were increased. In addition, melanogenesis stimulation did not induce cellular senescence.

These data indicate that melanogenesis stimulation of BF10 cells leads to alterations in metabolism and cell cycle progression that may contribute to an induction of cell quiescence, which may provide a mechanism of resistance against cellular injury promoted by melanin synthesis. Black-Right-Pointing-Pointer Melanogenesis inhibits cell proliferation, and induced cell cycle arrest in the G 1 phase. Black-Right-Pointing-Pointer Proteomic analysis showed alterations in proteins of the cell cycle and glucose metabolism.

Sustainability of a well-monitored salt iodization program in Iran: Two yr after legislation of salt iodization of 40 parts per million ppm in , goiter was still endemic and urinary iodine concentration UIC remained elevated in many provinces of Iran. Goiter prevalence and UIC were compared 2 and 7 yr after sustained consumption of uniformly iodized salt by Iranian households. Schoolchildren yr of all provinces were randomly selected by cluster sampling from December to June Goiter rate, UIC, and household salt iodine values were compared to those in Factory salt iodine was also compared in vs Ultrasonographically determined thyroid volumes of yr old children were compared in vs Here we present the first video demonstration of reduction corporoplasty in the management of phallic disfigurement in a 17 year old man with a history sickle cell disease and priapism.

Surgical management of aneurysmal dilation of the corpora has yet to be defined in the literature. We preformed bilateral elliptical incisions over the lateral corpora as management of aneurysmal dilation of the corpora to correct phallic disfigurement. The patient tolerated the procedure well and has resolution of his corporal disfigurement.

Reduction corporoplasty using bilateral lateral elliptical incisions in the management of aneurysmal dilation of the corpora is a safe an feasible operation in the management of phallic disfigurement. The review of modern ideas concerning the altered states of consciousness is presented in this article. Various methods of entry into the altered states of consciousness are looked over.

It is shown that the altered states of consciousness are insufficiently known, but important aspects of human being existence. The role of investigation of the altered states of consciousness for the creation of integrative scientific conception base is discussed.

Objective Here we present the first video demonstration of reduction corporoplasty in the management of phallic disfigurement in a 17 year old man with a history sickle cell disease and priapism. Introduction Surgical management of aneurysmal dilation of the corpora has yet to be defined in the literature. Results The patient tolerated the procedure well and has resolution of his corporal disfigurement.

Conclusions Reduction corporoplasty using bilateral lateral elliptical incisions in the management of aneurysmal dilation of the corpora is a safe an feasible operation in the management of phallic disfigurement. Nitrates are reduced to nitrogen gas by contacting the nitrates with a metal to reduce the nitrates to nitrites which are then contacted with an amide to produce nitrogen and carbon dioxide or acid anions which can be released to the atmosphere. Minor amounts of metal catalysts can be useful in the reduction of the nitrates to nitrites. Metal salts which are formed can be treated electrochemically to recover the metals.

Buccal alterations in diabetes mellitus. Long standing hyperglycaemia besides damaging the kidneys, eyes, nerves, blood vessels, heart, can also impair the function of the salivary glands leading to a reduction in the salivary flow. When salivary flow decreases, as a consequence of an acute hyperglycaemia, many buccal or oral alterations can occur such as: Buccal alterations found in diabetic patients, although not specific of this disease, have its incidence and progression increased when an inadequate glycaemic control is present. Linda Kieling, an art teacher at Rosemont Ridge Middle school in West Linn, Oregon, describes an altered book art project she introduced to her students.

Alteration of books is a form of recycling that started in the eleventh century when Italian monks recycled old manuscripts written on vellum by scraping off the ink and adding new text and…. Pancreatic cancer cells overexpressing Mucin 1 MUC1 rely on aerobic glycolysis and, correspondingly, are dependent on glucose for survival.

Our NMR metabolomics comparative analysis of control S Neo and MUC1-overexpressing S The observed alteration in glutamine metabolism under glucose limitation was accompanied by a relative decrease in the proliferation of MUC1-overexpressing cells compared with steady-state conditions. Moreover, glucose limitation induces G 1 phase arrest where S MUC1 cells fail to enter S phase and synthesize DNA because of a significant disruption in pyrimidine nucleotide biosynthesis. Our metabolomics analysis indicates that glutamine is the major source of oxaloacetate in S MUC1 cells, where oxaloacetate is converted to aspartate, an important metabolite for pyrimidine nucleotide biosynthesis.

However, glucose limitation impedes the flow of glutamine carbons into the pyrimidine nucleotide rings and instead leads to a significant accumulation of glutamine-derived aspartate in S Turbulent drag reduction for external flows. A summary of turbulent drag reduction approaches applicable to external flows is given. Because relatively recent and exhaustive reviews exist for laminar flow control and polymer hydrodynamic drag reduction , the focus here is upon the emerging areas of nonplanar geometry and large-eddy alteration.

Turbulent control techniques for air generally result in modest but technologically significant drag reductions order of 20 percent or less , whereas hydrodynamic approaches can yield drag reductions the order of 70 percent. Suggestions are included for alternative concepts and optimization of existing approaches. Paper presents a review and summary of turbulent drag reduction approaches applicable to external flows.

Because relatively recent and exhaustive reviews exist for laminar flow control and polymer hydrodynamic drag reduction , the paper focuses upon the emerging areas of nonplanar geometry and large eddy alteration. Turbulent control techniques for air generally result in modest but technologically significant drag reductions order of 20 percent or less whereas hydrodynamic approaches can yield drag reductions the order of 70 percent.

Paper also includes suggestions for alternative concepts and optimization of existing approaches. Faithful anaphase is ensured by Mis4, a sister chromatid cohesion molecule required in S phase and not destroyed in G 1 phase. The loss of sister chromatid cohesion triggers anaphase spindle movement.

We show that the fission yeast protein, Mis4, which is required for equal sister chromatid separation in anaphase is a different chromatid cohesion molecule that behaves independent of cohesin and is conserved from yeast to human. Its inactivation in G1 results in cell lethality in S phase and subsequent premature sister chromatid separation. Inactivation in G2 leads to cell death in subsequent metaphase—anaphase progression but missegregation occurs only in the next round of mitosis.

Mis4 is not essential for condensation, nor does it degrade in G1. Rather, it associates with chromosomes in a punctate fashion throughout the cell cycle. The mis4 mutation results in synthetic lethality with a DNA ligase mutant. Mis4 may form a stable link between chromatids in S phase that is split rather than removed in anaphase. A drift-diffusion checkpoint model predicts a highly variable and growth-factor-sensitive portion of the cell cycle G 1 phase. Even among isogenic cells, the time to progress through the cell cycle, or the intermitotic time IMT , is highly variable.

This variability has been a topic of research for several decades and numerous mathematical models have been proposed to explain it. Derivation and experimental comparison of cell-division probability densities. Here, we use the DDT modeling approach for both descriptive and predictive data analysis. We develop a custom numerical method for the reliable maximum likelihood estimation of model parameters in the absence of a priori knowledge about the number of detectable checkpoints.

We employ this method to fit different variants of the DDT model with one, two, and three checkpoints to IMT data from multiple cell lines under different growth conditions and drug treatments. We find that a two-checkpoint model best describes the data, consistent with the notion that the cell cycle can be broadly separated into two steps: The model predicts one part of the cell cycle to be highly variable and growth factor sensitive while the other is less variable and relatively refractory to growth factor signaling.

Using experimental data that separates IMT into G1 vs. S, G2, and M phases, we show that the model-predicted growth-factor-sensitive part of the cell cycle corresponds to a portion of G1, consistent with previous studies suggesting that the commitment step is the primary source of IMT variability.

These results demonstrate that a simple stochastic model, with just a handful of parameters, can provide fundamental insights into the biological underpinnings of cell cycle progression. The effects of phytoestrogens have been studied in the hypothalamic-pituitary-gonadal axis and in various non-gonadal targets. Epidemiologic and experimental evidence indicates a protective effect of phytoestrogens also in colorectal cancer. The mechanism through which estrogenic molecules control colorectal cancer tumorigenesis could possibly involve estrogen receptor beta, the predominantly expressed estrogen receptor subtype in colon mucosa.

To validate this hypothesis, we therefore used an engineered human colon cancer cell line induced to overexpress estrogen receptor beta, beside its native cell line, expressing very low levels of ERbeta and not expressing ERalpha; as a phytoestrogenic molecule, we used kaempferide triglycoside, a glycosylated flavonol from a Dianthus caryophyllus cultivar. The inhibitory properties of this molecule toward vegetal cell growth have been previously demonstrated: Kaempferide triglycoside proved to inhibit the proliferation of native and estrogen receptor beta overexpressing colon cancer cells through a mechanism not mediated by ligand binding dependent estrogen receptor activation.

Interestingly, the biological effects of this kaempferide triglycoside were strengthened by the presence of high levels of estrogen receptor beta. Pleiotropic molecular effects of phytoestrogens may explain their protective activity against colorectal cancer and may represent an interesting area for future investigation with potential clinical applications.

The cancer chemopreventive property of Chinese herb new isolate isorhapontigenin ISO and mechanisms underlying its activity have never been explored. Further studies showed that ISO treatment resulted in cyclin D1 downregulation in dose- and time-dependent manner. Our results demonstrated that ISO is a promising chemopreventive agent via upregulating mkp-1 mRNA stability, which is distinct from its cancer therapeutic effect with downregulation of XIAP and cyclin D1 expression.

Attention Alters Perceived Attractiveness. Can attention alter the impression of a face? Previous studies showed that attention modulates the appearance of lower-level visual features. For instance, attention can make a simple stimulus appear to have higher contrast than it actually does. We tested whether attention can also alter the perception of a higher-order property-namely, facial attractiveness. We asked participants to judge the relative attractiveness of two faces after summoning their attention to one of the faces using a briefly presented visual cue.

Across trials, participants judged the attended face to be more attractive than the same face when it was unattended. This effect was not due to decision or response biases, but rather was due to changes in perceptual processing of the faces. These results show that attention alters perceived facial attractiveness, and broadly demonstrate that attention can influence higher-level perception and may affect people's initial impressions of one another.

Digital noise reduction schemes are being used in most hearing aids currently marketed. Although most are modulation-based schemes ie, differentiating speech from noise based on temporal characteristics , spectral subtraction techniques are being applied as well.

The purpose of this article is to overview these schemes in terms of their differences and similarities. It's important to understand what breast reduction surgery entails — including possible risks and complications — as Immunization alters body odor. Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice.

Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated RV and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus WNV vaccine compared with urine of corresponding controls.

These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide LPS; a general elicitor of innate immunological responses from the urine of control mice.

Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: Published by Elsevier Inc. To evaluate a series of case that developed iris changes after performing Descemet's stripping automated endothelial keratoplasty DSAEK.

Retrospective study of eyes that developed iris abnormalities, such as pupil ovalisation, iris atrophy, iridocorneal synechiae, mydriatic pupil, and pigmentary changes after performing DSAEK in a tertiary hospital. In a series of the first 32 DSAEK procedures performed, new single or mixed iris alterations were observed in 12 eyes Iris-corneal synechiae were observed in 7 eyes, corectopias in 9 eyes, iris atrophy in 3 cases, and one case developed an areflexic mydriatic pupil. Long-term pigment dispersion at the edge of the lenticule was observed in 12 eyes.

The alterations occurred after three months from the surgery. In the evaluation of the associated factors, malignant glaucoma had occurred in 1 case, 2 eyes had required a second surgery, one case by re-DSAEK, and the other one by removing the intraocular lens due to lens opacification. Two cases had a shallow anterior chamber.

No relationship was found between the thickness of the peripheral lenticule and the presence of synechiae. A discussion is presented on the relationship between increased intraocular pressure due to air in anterior chamber and its relationship with ischaemia and secondary alterations in the iris.

Altered -stress fracturing is a concept whereby a hydraulic fracture in one well is reoriented by another hydraulic fracture in a nearby location. The application is in tight, naturally fractured, anisotropic reservoirs in which conventional hydraulic fractures parallel the highly permeable natural fractures and little production enhancement is achieved by conventional hydraulic fracturing. Altered -stress fracturing can modify the stress field so that hydraulic fractures propagate across the permeable natural fractures. A field test was conducted in which stress changes of to psi 1.

These results show that stress- altered fracturing is possible at this site and others. Analytic and finite element calculations quantify the effects of layers, stresses, and crack size. Reservoir calculations show significant enhancement compared to conventional treatments. Hindlimb unloading alters ligament healing. We investigated the hypothesis that hindlimb unloading inhibits healing in fibrous connective tissue such as ligament. Male rats were assigned to 3- and 7-wk treatment groups with three subgroups each: Ambulatory and suspended animals underwent surgical rupture of their medial collateral ligaments, whereas sham surgeries were performed on control animals.

During mechanical testing, most suspended ligaments failed in the scar region, indicating the greatest impairment was to ligament and not to bone-ligament insertion. Ligament testing revealed significant reductions in maximum force, ultimate stress, elastic modulus, and low-load properties in suspended animals. In addition, femoral mineral density, femoral strength, gastrocnemius mass, and tibialis anterior mass were significantly reduced.

Microscopy revealed abnormal scar formation and cell distribution in suspended ligaments with extracellular matrix discontinuities and voids between misaligned, but well-formed, collagen fiber bundles.

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Hence, stress levels from ambulation appear unnecessary for formation of fiber bundles yet required for collagen to form structurally competent continuous fibers. Results support our hypothesis that hindlimb unloading impairs healing of fibrous connective tissue. In addition, this study provides compelling morphological evidence explaining the altered structure-function relationship in load-deprived healing connective tissue.

Altered States of Consciousness. Medicine, sex, and religion are presented as related areas of human thought and behavior in which people traditionally have sought temporary release from daily living. In essence, these areas represent a search for altered states of consciousness. The harmful way is through drug addiction. Five common characteristics are cited for the three areas. Examples of their universality are traceable by their omnipresence and their appearance in most childhood games—especially those taking on sexual nuances—which are usually hidden from adults.

If Eastern knowledge and control of bodily processes were geared to Western technology, mankind would benefit. Genetically Altered Plant Species. Researchers in Robert Ferl's lab at the University of Florida in Gainesville, genetically altered this Arabdopsis Thaliana a brassica species plant to learn how extreme environments, such as the low atmospheric pressure on Mars, affect plant genes.

When those genes were turned on after exposure to reduced atmospheric pressure, GFP was turned on as well, causing cells expressing those genes to glow green under a blue light. The natural fluorescence of chlorophyll accounts for the red glow. Thermal remediation alters soil properties - a review.

Contaminated soils pose a risk to human and ecological health, and thermal remediation is an efficient and reliable way to reduce soil contaminant concentration in a range of situations. A primary benefit of thermal treatment is the speed at which remediation can occur, allowing the return of treated soils to a desired land use as quickly as possible. However, this treatment also alters many soil properties that affect the capacity of the soil to function. While extensive research addresses contaminant reduction , the range and magnitude of effects to soil properties have not been explored.

Understanding the effects of thermal remediation on soil properties is vital to successful reclamation, as drastic effects may preclude certain post-treatment land uses. This review highlights thermal remediation studies that have quantified alterations to soil properties, and it supplements that information with laboratory heating studies to further elucidate the effects of thermal treatment of soil. Notably, both heating temperature and heating time affect i soil organic matter; ii soil texture and mineralogy; iii soil pH; iv plant available nutrients and heavy metals; v soil biological communities; and iv the ability of the soil to sustain vegetation.

Broadly, increasing either temperature or time results in greater contaminant reduction efficiency, but it also causes more severe impacts to soil characteristics. Thus, project managers must balance the need for contaminant reduction with the deterioration of soil function for each specific remediation project. Nanosized aluminum altered immune function. On the basis of their uses in jet fuels and munitions, the most likely scenario for aluminum nanoparticle NP exposure is inhalation.

NPs have been shown to be capable of penetrating deep into the alveolar regions of the lung, and therefore human alveolar macrophages U with human type II pneumocytes A were cultured together and exposed to NPs dispersed in an artificial lung surfactant to more accurately mimic the lung microenvironment.

Two types of NPs were evaluated: Following a h incubation, cell viability was assessed using MTS, and mild toxicity was observed at higher doses with the U cells affected more than the A Since the U cells provided protection from NP toxicity, the cocultures were exposed to a benign concentration of NPs and infected with the respiratory pathogen community-associated methicillin-resistant Staphylococcus aureus ca-MRSA to determine any changes in cellular function. Phagocytosis assays demonstrated that the NPs impaired phagocytic function, and bacterial growth curves confirmed that this reduction in phagocytosis was not related to NP-bacteria interactions.

Therefore, although the NPs were not toxic to the cells, they did impair the cell's natural ability to respond to a respiratory pathogen regardless of NP composition. The widespread deployment of Automated Fingerprint Identification Systems AFIS in law enforcement and border control applications has heightened the need for ensuring that these systems are not compromised.

While several issues related to fingerprint system security have been investigated, including the use of fake fingerprints for masquerading identity, the problem of fingerprint alteration or obfuscation has received very little attention. Fingerprint obfuscation refers to the deliberate alteration of the fingerprint pattern by an individual for the purpose of masking his identity. Several cases of fingerprint obfuscation have been reported in the press. Fingerprint image quality assessment software e. The main contributions of this paper are: Experimental results show the feasibility of the proposed approach in detecting altered fingerprints and highlight the need to further pursue this problem.

Genetic Alterations in Glioma. Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas the most common and aggressive subtype of glioma.

This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively.

Immersive environments provide an exciting experiential technology to visualize the natural world. Given the increasing accessibility of o cameras and virtual reality headsets we are now able to visualize artistic principles and scientific concepts in a fully immersive environment. The technology has become popular for photographers as well as designers, industry, educational groups, and museums.

Here we show a sci-art perspective on the use of optics and light in the capture and manipulation of o images and video of geologic phenomena and cultural heritage sites in Alaska, England, and France. Additionally, we will generate intentionally altered perspectives to lend a surrealistic quality to the landscapes. Some o view cameras now use small portable dual lens technology extending beyond the o fish eye lens previously used, providing better coverage and image quality.

Virtual reality headsets range in level of sophistication and cost, with the most affordable versions using smart phones and Google Cardboard viewers. The equipment used in this presentation includes a Ricoh Theta S spherical imaging camera. Here we will demonstrate the use of o imaging with attendees being able to be part of the immersive environment and experience our locations as if they were visiting themselves. Altered Global Signal Topography in Schizophrenia. Schizophrenia SCZ is a disabling neuropsychiatric disease associated with disruptions across distributed neural systems.

Resting-state functional magnetic resonance imaging has identified extensive abnormalities in the blood-oxygen level-dependent signal in SCZ patients, including alterations in the average signal over the brain-i. It remains unknown, however, if these "global" alterations occur pervasively or follow a spatially preferential pattern. This study presents the first network-by-network quantification of GS topography in healthy subjects and SCZ patients.

We observed a nonuniform GS contribution in healthy comparison subjects, whereby sensory areas exhibited the largest GS component. In SCZ patients, we identified preferential GS representation increases across association regions, while sensory regions showed preferential reductions. GS representation in sensory versus association cortices was strongly anti-correlated in healthy subjects. This anti-correlated relationship was markedly reduced in SCZ.

The plasma CAB concentration at the time of virus challenge appeared to be more important for protection than sustaining therapeutic plasma concentrations with the second CAB long acting injection. Design and patients Ninety-eight previously untreated acromegalics were recruited into this prospective multicentre study. A total of 68 patients successfully completed 48 weeks of the study period, received 12 doses of octreotide LAR 10—30 mg every 4 weeks, and constituted the population used for this analysis.

Measurements and results A clinically relevant reduction i. A reduction in the severity of symptoms of acromegaly was observed early in treatment and was maintained throughout the study period. Conclusion Octreotide LAR represents a viable alternative to surgery for primary treatment of acromegaly leading to a progressive regression of tumour volume, a sustained control of biochemical abnormalities and an adequate relief of symptoms of the disease.

Modification with poly ethylene glycol PEG is a widely used method for the prolongation of plasma half-life of colloidal carrier systems such as nanoparticles prepared from human serum albumin HSA. However, the quantification of the PEGylation extent is still challenging. Moreover, the influence of different PEG derivatives, which are commonly used for nanoparticle conjugation, has not been investigated so far.

A size exclusion chromatography method with refractive index detection was established which enabled the quantification of unreacted PEG in the supernatant. The achieved results were confirmed using a fluorescent PEG derivative, which was detected by photometry and fluorimetry. By incubating the nanoparticles with fetal bovine serum the reduced adsorption of serum proteins on PEGylated HSA nanoparticles compared to non- PEGylated HSA nanoparticles was demonstrated using sodium dodecylsulfate polyacrylamide gel electrophoresis.

Finally, the positive effect of PEGylation on plasma half-life was demonstrated in an in vivo study in mice. Compared to unmodified nanoparticles the PEGylation led to a four times larger plasma half-life. Switching long acting antipsychotic medications to aripiprazole long acting once-a-month: Aripiprazole long acting once-monthly AOM is a long acting atypical antipsychotic with proven efficacy in schizophrenia and with a pharmacological and a side effect profile that is different from other antipsychotics.

These and other characteristics make AOM a possible alternative in patients requiring a change in long acting antipsychotic treatment due to issues such as lack of efficacy or persistent side effects. Both clinical and pharmacological factors should be considered when switching antipsychotics, and specific guidelines for long acting antipsychotic switching that address all these factors are needed.

A panel of Italian and Spanish experts in psychiatry met to discuss the strategies for the switch to AOM in patients with schizophrenia. Real life clinical experiences were shared and the clinical strategies to improve the likelihood of success were discussed. Due to its specific pharmacological and tolerability profile, AOM represents a suitable alternative for patients with schizophrenia requiring a switch to a new LAI treatment because of lack of efficacy or persistent side effects from another LAI. Possible strategies for the switch to AOM are presented in this expert consensus paper in an attempt to provide guidance throughout the entire switching process.

Delayed release formulation of the somatostatin analog RC inhibits the growth hormone GH response to GH -releasing factor- NH2 and decreases elevated prolactin levels in rats. Recently, we have developed a long-acting delivery system for our somatostatin SS analog RC based on injectable microcapsules in poly- D,L-lactide-coglycolide. Male rats anesthetized with pentobarbital were injected iv with 2. The GRF stimuli were repeated 48 h, 96 h, and 8 days after administration of SS analog in microcapsules.

The GH levels augmented by pentobarbital were also decreased by the RC microcapsules P less than 0. Animals treated with microcapsules showed smaller increases in their body weight than untreated rats P less than 0. We also investigated the effect of RC microcapsules on hyperprolactinemic female rats implanted with pituitary glands under the kidney capsules. High PRL levels in rats bearing pituitary grafts showed a significant decrease when measured 4 days after the administration of RC microcapsules.

These results demonstrate the efficacy of the long-acting delivery system of the SS analog RC and suggest the possible clinical usefulness of this formulation for lowering GH and PRL levels. Recent advances in COPD disease management with fixed-dose long-acting combination therapies. Combinations of two long-acting bronchodilators and long-acting bronchodilators with inhaled corticosteroids ICS are recommended therapies in the management of chronic obstructive pulmonary disease COPD.

No new safety concerns have been observed with combinations of long-acting bronchodilators. Combinations of two long-acting bronchodilators represent a new and convenient treatment option in COPD. The most common initial prescriptions of long-acting opioids were fentanyl patch Long-acting insulins alter milk composition and metabolism of lactating dairy cows.

This study investigated the effect of 2 different types of long-acting insulin on milk production, milk composition, and metabolism in lactating dairy cows. The H and L treatments were administered twice daily at h intervals via subcutaneous injection for 10d. Cows were milked twice daily, and milk composition was determined every other day.

Mammary biopsies were conducted on d 11, and mammary proteins extracted from the biopsies were analyzed by Western blot for components of insulin and mammalian target of rapamycin signaling pathways. Treatment had no effect on dry matter intake or milk yield. Treatment with both forms of long-acting insulin increased milk protein content and tended to increase milk protein yield over the d treatment period. Analysis of milk N fractions from samples collected on d 10 of treatment suggested that cows administered L tended to have higher yields of milk protein fractions than cows administered H.

Milk fat content and yield tended to be increased for cows administered long-acting insulins. Lactose content and yields were decreased by treatment with long-acting insulins. Administration of long-acting insulins, particularly L, tended to shift milk fatty acid composition toward increased short- and medium-chain fatty acids and decreased long-chain fatty acids. Plasma concentrations of glucose and urea N were lower for cows administered long-acting insulins; interactions of treatment and sampling time were indicative of more pronounced effects of L than H on these metabolites.

Concentrations of nonesterified fatty acids and insulin were increased in cows administered long-acting insulins. Decreased concentrations of urea N in both plasma and milk suggested more efficient use of N in cows. Effects of a long acting somatostatin analog on pituitary, adrenal, and testicular function during rest and acute exercise: The purpose of this study was to delineate the possible endocrine effects of exercise-induced GH secretion.

Twelve healthy adult males were studied during short 20 min and subsequent prolonged 2 h physical exercise and recovery period 2 h , both after injection of a long acting somatostatin analog [Sandostatin ST ; 0. Additional subjects were studied during rest with similar injections of ST 0. Several venous blood samples were taken during the trials and analyzed for selected hormones, monitoring pituitary, testicular, and adrenal functions.

ST injection blocked the serum GH response to short term maximal bicycle ergometer exercise, but not to the following prolonged bicycle exercise. No relationship of the exercise-associated GH increase to the concomitant endocrine responses of the adrenals and testes was observed. Unexpectedly, the higher ST doses 0.

This review describes the positive effects of growth hormone GH on the cardiovascular system. We analyze why the vascular endothelium is a real internal secretion gland, whose inflammation is the first step for developing atherosclerosis, as well as the mechanisms by which GH acts on vessels improving oxidative stress imbalance and endothelial dysfunction.

long-acting pegylated gh: Topics by theranchhands.com

We also report how GH acts on coronary arterial disease and heart failure, and on peripheral arterial disease, inducing a neovascularization process that finally increases flow in ischemic tissues. We include some preliminary data from a trial in which GH or placebo is given to elderly people suffering from critical limb ischemia, showing some of the benefits of the hormone on plasma markers of inflammation, and the safety of GH administration during short periods of time, even in diabetic patients.

We also analyze how Klotho is strongly related to GH , inducing, after being released from the damaged vascular endothelium, the pituitary secretion of GH , most likely to repair the injury in the ischemic tissues. We also show how GH can help during wound healing by increasing the blood flow and some neurotrophic and growth factors. In summary, we postulate that short-term GH administration could be useful to treat cardiovascular diseases. Models of health behaviour predict intention to use long-acting reversible contraception. A questionnaire was completed by a convenience sample of women attending a community sexual health clinic.

The independent variables were constructs of theory of planned behaviour attitude, subjective norm and perceived behavioural control and health belief model perceived susceptibility, perceived severity, perceived benefits, perceived barriers, health motivation and cues to action. The dependent variable was intention to use long-acting reversible contraception. Perceived behavioural control, perceived barriers and health motivation predict the use of long-acting reversible contraception. Public health information for women considering using long-acting reversible contraception should be based around addressing the perceived barriers and promoting long-acting reversible contraception as a reliable contraceptive method.

Uptake of long-acting reversible contraceptive devices in Western region of The Gambia. The contraceptive method has become an essential factor in the life of most women of reproductive age group; although it varies in different stages of their life course. The use of long acting reversible methods LARC is proposed as a strategy to reverse undesirable maternal health consequences in developing countries. To determine the uptake of long-acting reversible contraceptive in The Gambia.

A community based cross-sectional study of women attending family planning clinic were studied using intervieweradministered questionnaire which included information on socio-demographic factors, reproductive health and contraceptive use of the participants. Of the three commonly available long acting reversible contraceptive methods, Depo Provera was the most commonly used method; 78 of Being housewives, with living children and having secondary level education were associated with high uptake of LARC. The uptake of long acting reversible contraceptive was high; with Depo Provera as the most commonly used contraceptive method in The Gambia.

There seemed to be an increase in the uptake of implants; with intrauterine contraceptive device being the least commonly used method. Development of a neuromedin U-human serum albumin conjugate as a long-acting candidate for the treatment of obesity and diabetes. Comparison with the PEGylated peptide. Neuromedin U NMU is an endogenous peptide implicated in the regulation of feeding, energy homeostasis, and glycemic control, which is being considered for the therapy of obesity and diabetes.

A key liability of NMU as a therapeutic is its very short half-life in vivo. We show here that conjugation of NMU to human serum albumin HSA yields a compound with long circulatory half-life, which maintains full potency at both the peripheral and central NMU receptors. Initial attempts to conjugate NMU via the prevalent strategy of reacting a maleimide derivative of the peptide with the free thiol of Cys34 of HSA met with limited success, because the resulting conjugate was unstable in vivo.

Use of a haloacetyl derivative of the peptide led instead to the formation of a metabolically stable conjugate. Collectively, our results reinforce the notion that NMU-based therapeutics are promising candidates for the treatment of obesity and diabetes. Consequences of stopping growth hormone GH therapy in young GH deficient patients with childhood onset disease. Many studies have shown the beneficial, anabolic effects of growth hormone GH replacement therapy in GH deficient adults with childhood onset or adult onset disease.

It is becoming increasingly evident, however, that these two groups of patients differ in many respects. Patients with adult onset GH deficiency represent fully developed individuals who have various organic, cerebral defects. By contrast, patients with childhood onset disease represent a heterogenous group comprising individuals with conditions, such as idiopathic isolated GH deficiency, genetic defects and organic defects.

It is unclear whether continued treatment with GH in childhood onset GH deficiency will yield results as positive as those seen in trials where GH is re-instituted after longer periods without treatment. Similarly, it is unknown at what timepoint cessation of GH treatment will cause a worsening in the physical state of the patient. In our placebo-controlled trial where GH was discontinued in 19 patients treated with GH during childhood, we determined exercise capacity, body composition, muscle mass and strength, cardiac function, sweating capacity, thyroid function and glucose metabolism before and after 12 months of continued treatment with GH.

Silk has a robust clinical track record and is emerging as a promising biopolymer for drug delivery, including its use as nanomedicine. However, silk-based nanomedicines still require further refinements for full exploitation of their potential; the application of "stealth" design principals is especially necessary to support their evolution. The aim of this study was to develop and examine the potential of PEGylated silk nanoparticles as an anticancer drug delivery system.

We first generated B. We then surface grafted polyethylene glycol PEG to the fabricated silk nanoparticles and verified the aqueous stability and morphology of the resulting PEGylated silk nanoparticles. We assessed the drug loading and release behavior of these nanoparticles using clinically established and emerging anticancer drugs. Finally, we demonstrated significant cytotoxicity of drug loaded silk nanoparticles applied as single and combination nanomedicines to human breast cancer cells. In conclusion, these results, taken together with prior silk nanoparticle data, support a viable future for silk-based nanomedicines.

Here, we present a thorough study of pegylated silica nanoparticle SNP interaction with different biological environments. The SNPs have a mean diameter of about 40 nm and are coated with polyethylene glycol PEG of different molecular weights. The physicochemical characterization of SNPs allowed the confirmation of the binding of PEG chains to the silica surface, the reproducibility of the synthesis and the narrow size-dispersion.

In view of clarifying the SNP interaction with biological environments, we first assessed the SNP reactivity after the incubation with two cell lines macrophages RAW Then, we investigated the effect of the protein adsorption on the SNP surface using the model serum protein, bovine serum albumin BSA. We found that the protein adsorption takes place more heavily on poorly pegylated SNPs, promoting the uptake of the latter by macrophages and leading to an increased mortality of these cells.

To better understand this mechanism by means of flow cytometry, the dye Ru bpy 3Cl2 was incorporated in the SNPs. The overall results highlight the SNP potentialities as a drug delivery system, thanks to the low interactions with the macrophages. Formulation and PEGylation optimization of the therapeutic PEGylated phenylalanine ammonia lyase for the treatment of phenylketonuria. Phenylketonuria PKU is a genetic metabolic disease in which the decrease or loss of phenylalanine hydroxylase PAH activity results in elevated, neurotoxic levels of phenylalanine Phe.

Due to many obstacles, PAH enzyme replacement therapy is not currently an option. However, issues regarding immunogenicity, enzyme production and mode of delivery needed to be overcome. Through the evaluation of PAL enzymes from multiple species, three potential PAL enzymes from yeast and cyanobacteria were chosen for evaluation of their therapeutic potential.

L-Phe and trans-cinnamate were identified as activity stabilizing excipients. The mechanisms underlying these disturbances have not been fully elucidated. The mechanism of action of GHRP-6 is unknown, but it probably acts by inhibiting the effects of somatostatin on GH release. Our data suggest that thyroid hormones modulate GH release induced by these two peptides in a differential way.

Bipolar I disorder is a serious and disabling psychiatric illness. It is associated with a significant reduction in quality of life and an increased risk for suicide. Pharmacotherapy is essential for both the acute and maintenance treatment of bi-polar I disorder. While multiple oral medications are recommended for the maintenance treatment, there are not many long-acting injectable medications approved for this indication.

New treatments that would improve patient adherence have the potential for decreasing relapses and improving patients' ability to remain functional members of society. In this paper we discuss the available data for safety and efficacy of aripiprazole long-acting injectable in bipolar disorder. Models of GH deficiency in animal studies.

003 Spiritual Counseling Room Noriko who hates her own looks (Japanese Edition)

Growth hormone GH is a peptide hormone released from pituitary somatotrope cells that promotes growth, cell division and regeneration by acting directly through the GH receptor GHR , or indirectly via hepatic insulin-like growth factor 1 IGF1 production. GH deficiency GHD can cause severe consequences, such as growth failure, changes in body composition and altered insulin sensitivity, depending of the origin, time of onset childhood or adulthood or duration of GHD.

The highly variable clinical phenotypes of GHD can now be better understood through research on transgenic and naturally-occurring animal models, which are widely employed to investigate the origin, phenotype, and consequences of GHD, and particularly the underlying mechanisms of metabolic disorders associated to GHD. Here, we reviewed the most salient aspects of GH biology, from somatotrope development to GH actions, linked to certain GHD types, as well as the animal models employed to reproduce these GHD-associated alterations. Growth hormone GH -independent stimulation of adiposity by GH secretagogues.

Here we compared the effects of twice daily s. GH treatment markedly enhanced body weight in both groups. Copyright Academic Press. Regulatory challenges in developing long-acting antiretrovirals for treatment and prevention of HIV infection. To outline some of the regulatory challenges inherent to the development of long-acting antiretrovirals ARVs for the treatment or prevention of HIV infection. Despite advances in drug development that have reduced ARV dosing to once daily, suboptimal drug adherence remains an obstacle to successful HIV treatment.

Further, large randomized trials of once daily oral ARVs for preexposure prophylaxis PrEP have shown that drug adherence correlates strongly with prophylactic effect and study outcomes. Thus, the prospect of developing long-acting ARVs, which may mitigate drug adherence issues, has attracted considerable attention lately.

Because of their pharmacokinetic properties, the development of long-acting ARVs can present novel regulatory challenges. Chief among them is determining the appropriate dosing regimen, the need for an oral lead-in, and whether existing data with an approved oral agent, if available, can be leveraged for a treatment or prevention indication.

For PrEP, because validated biomarkers are lacking, additional nonclinical studies and evaluation of tissue concentrations in multiple compartments may be necessary to identify optimal dosages. Study design and choice of controls for registrational trials of new long-acting PrEP agents might also prove challenging following the availability of an oral PrEP drug. Differences in acute anorectic effects of long-acting GLP-1 receptor agonists in rats. Long-acting glucagon-like peptide-1 receptor GLP-1R agonists have both glucose- and weight-lowering effects. The brain is poised to mediate both of these actions since GLP-1Rs are present in key areas known to control weight and glucose.

Although some research has been performed on the effects of Both short- and long-acting formulations of oxytetracycline are commonly used in veterinary medicine to treat animals infected with gram-negative and gram-positive bacteria, rickettsiae, mycoplasma, and chlamydiae. To compare pharmacokinetics of short- and long-acting oxytetracycline in chickens, injectable formulations from the same pharmaceutical company were administered to healthy 6-week-old broiler chickens in accordance to the labeled instructions.

Fourteen chickens were separated into 2 groups: Blood samples were collected into heparinized tubes before and at 0. Thereafter, blood samples were taken every 24 hours up to hours. Plasma concentrations of oxytetracycline were determined by competitive enzyme-linked immunoabsorbent assay, and pharmacokinetic parameters were obtained. However, considering the additional labor, patient stress, and mortalities associated with handling, in addition to rejection of the carcass due to tissue necrosis resulting from multiple injections, we recommend use of the long-acting instead of the short-acting injectable formulation in broiler chickens.

Height and weight were measured monthly during the…. Background Long-acting risperidone for injection is a second-generation antipsychotic indicated for the treatment of schizophrenia and related psychotic disorders. It is a relatively new agent with pharmacokinetic and dosing properties unlike those of conventional long-acting antipsychotic drugs administered by injection. Objective To determine the proportion of patients for whom long-acting risperidone for injection was prescribed appropriately in acute care settings in the Fraser Health Authority of British Columbia, according to the following 4 criteria: A variety of other variables, including documented approval under special authority from the provincial drug coverage program, length of hospital stay, initial dose of risperidone, and total number of doses, were assessed as secondary outcomes.

Methods A chart review was conducted for all patients for whom therapy with long-acting risperidone for injection was prescribed during stays in 8 acute care hospitals between July 1, , and July 22, The appropriateness of prescribing was assessed according to the 4 prespecified criteria. Results Long-acting risperidone for injection was prescribed for patients during the study period, and 82 of these started therapy and were included in the evaluation.

The primary outcome could not be assessed for 27 of these 82 patients, because they were discharged early, and data for some or all of the 4 criteria were not available. Premature escalation of the dose and inadequate overlap with antipsychotic supplementation. Effects of PEGylation on biomimetic synthesis of magnetoferritin nanoparticles. Recent studies have demonstrated that ferrimagnetic magnetoferritin nanoparticles are a promising novel magnetic nanomaterial in biomedical applications, including biocatalysis, imaging, diagnostics, and tumor therapy.

Here we investigated the PEGylation of human H-ferritin HFn proteins and the possible influence on biomimetic synthesis of magnetoferritin nanoparticles. The PEGylated HFn proteins were used for biomimetic synthesis of ferrimagnetic magnetoferritin nanoparticles. We found that, compared with magnetoferritin using non- PEGylated HFn protein templates, the synthesized magnetoferritin using the PEGylated HFn protein templates possessed larger magnetite cores, higher magnetization and relaxivity values, and improved thermal stability. These results suggest that the PEGylation of H-ferritin may improve the biomineralization of magnetoferritin nanoparticles and enhance their biomedical applications.

Background Risperidone long-acting injectable was previously approved for treatment of schizophrenia as biweekly injections in the gluteal muscle only. We present data on local injection-site tolerability and safety of risperidone long-acting injectable and comparability of systemic exposure of deltoid versus gluteal injections. The pharmacokinetic results from both the studies have already been published. However, none of the discontinuations were due to injection-site related reasons.

The percent upper confidence limit of the true proportion of injection-site issue withdrawals was 5. No moderate or severe injection-site reactions were reported. Conclusion Intramuscular injections via the deltoid and gluteal sites are equivalent routes of administration of risperidone long-acting injectable with respect to local injection-site tolerability.

The overall safety and tolerability profile of risperidone long-acting injectable was comparable when administered as an intramuscular injection in the deltoid Testing the effects of long-acting steroids in edema and ecchymosis after closed rhinoplasty. Steroids have proven to be of some benefit in rhinoplasty edema and ecchymosis when administered at a high and repeated dose. To evaluate the effects of single-dose, long-acting intramuscular steroids on postoperative edema and ecchymosis after closed rhinoplasty with osteotomies compared with placebo.

A randomized, double-blinded, placebo-controlled trial was performed. Fifty-four patients were randomly assigned to two groups: The same surgeon performed all surgeries, with patients under general anesthesia. Acetaminophen was the only analgesic used to control postoperative pain. High-resolution digital photographs were taken on postoperative days 1, 3, 7 and Scoring was performed separately for eyelid swelling and ecchymosis by an independent observer using a graded scale 0 to 5 for edema and a scoring system 0 to 13 for ecchymosis.

No statistically significant differences in terms of age, sex or amount of bleeding during surgery were found between the two groups. No statistically significant difference was observed in the decrease of both ecchymosis and edema between placebo and high-dose, long-acting dexamethasone. A statistically significant difference in operation time was found, favouring the steroid group. No severe complications were observed due to steroid use.

Osteotomies are basically a form of controlled trauma, with considerable disruption of the abundant blood vessels in this facial region and, therefore, are associated with with undesirable effects. A recent meta-analysis failed to show benefits of the use of steroids after postoperative day 3. Only a trend toward reduction in edema and ecchymosis with the use of long-acting steroids compared with placebo was demonstrated in the present study. Of the multiple theories to explain exceptional longevity, the most robust of these has centered on the reduction of three anabolic protein hormones, growth hormone GH , insulin-like growth factor, and insulin.

Mitochondrial metabolism is upregulated in the absence of GH , whereas in GH transgenic mice and dwarf mice treated with GH , multiple aspects of these pathways are suppressed. Elevated adiponectin, a key antiinflammatory cytokine, is also very likely to contribute to longevity in these mice. Thus, several important components related to energy metabolism are altered in GH mutant mice, and these differences are likely critical in aging processes and life-span extension. GH secretion peaks at puberty and continues to be secreted in adulthood, albeit at a declining rate. Profound GH deficiency GHD in adults with pituitary disease is associated with symptoms that improve with GH substitution, but it is important to tailor the GH dose to avoid overtreatment.

The objective of the study was to identify novel serum biomarkers of GH treatment in adults with GHD. Eight patients with profound GHD as a consequence of a pituitary adenoma or its treatment were evaluated before and 3 months after GH replacement therapy 0. Serum proteomic changes were studied using two-dimensional gel electrophoresis and mass spectrometry. Protein profiles were analyzed and compared in serum samples obtained before and after GH treatment.

The levels of six serum protein spots were significantly altered after GH substitution. These proteins were identified as five isoforms of haptoglobin decreased in posttreatment samples and one isoform of apolipoprotein A-I increased in posttreatment samples. Importantly, changes in the levels of the identified proteins were associated with decreases in fat mass and increases in lean mass in all patients. These results were independent of serum IGF-I levels. Implications for GH Signaling.

GH signaling yields multiple anabolic and metabolic effects. Physiological implications of this new model are discussed. Knowledge of this relationship is important to correlate pretreatment levels that best predict response to treatment. To monitor tumor activity and tumor viability requires measurement of GH levels. The objective of this study was to investigate the efficiency of uptake of PEGylated polylactide-co-gycolide PLGA nanoparticles by breast cancer cells.

The nanoparticles were loaded with coumarin-6 C6 as a fluorescence marker. The particles were characterized for surface morphology, particle size, zeta potential, and for cellular uptake by 4T1 murine breast cancer cells. Irrespective of the amount of PEG, all formulations yielded smooth spherical particles.

However, a comparison of the particle size of various formulations showed bimodal distribution of particles. Each formulation was later passed through a 1. The protein corona of circulating PEGylated liposomes. Following systemic administration, liposomes are covered by a 'corona' of proteins, and preserving the surface functionality is challenging. Coating the liposome surface with polyethylene glycol PEG is the most widely used anti-opsonization strategy, but it cannot fully preclude protein adsorption.

To date, protein binding has been studied following in vitro incubation to predict the fate of liposomes in vivo, while dynamic incubation mimicking in vivo conditions remains largely unexplored. The main aim of this investigation was to determine whether shear stress, produced by physiologically relevant dynamic flow, could influence the liposome-protein corona.

The corona of circulating PEGylated liposome was thoroughly compared with that formed by incubation in vitro. Size of coronas formed under static vs. On the other side, the corona of circulating liposomes was more negatively charged than its static counterpart. Of note, the variety of protein species in the corona formed in a dynamic flow was significantly wider.

Collectively, these results demonstrated that the corona of circulating PEGylated liposomes can be considerably different from that formed in a static fluid. This seems to be a key factor to predict the biological activity of a liposomal formulation in a physiological environment. Opioid therapy is an increasingly used modality for treatment of musculoskeletal pain despite multiple associated risks. The purpose of this study was to evaluate how preoperative opioid use affects early outcomes after total joint arthroplasty.

A total of patients undergoing total joint arthroplasty were matched by age, gender, and procedure into 3 groups stratified by preoperative opioid use nonuser, short acting [eg, Vicodin], long acting [eg, Oxycontin]. Compared to nonusers, preoperative long-acting use was associated with increased postoperative mean opioid consumption 46 mg vs mg mean morphine equivalents, P Initiation and continuation of long-acting reversible contraception in the United States military healthcare system. Long-acting reversible contraception is more effective for pregnancy prevention than shorter-acting contraceptive methods and has the potential to reduce healthcare disparities and costs.

However, long-acting reversible contraception is underused in the United States. One population of interest is beneficiaries of the United States military healthcare system who have access to universal healthcare, including no-cost, no-copay contraception with unlimited method switching, and comprise a large, actual use cohort. Efforts to increase long-acting reversible contraception initiation and continuation in this population may improve health outcomes and mitigate the profound consequences of unintended or mistimed pregnancy on readiness and cost to the military.

We aimed to determine long-acting reversible contraception initiation and continuation rates among the diverse population with universal healthcare who are enrolled in the US military healthcare system. Individuals were assessed for long-acting reversible contraception initiation and continuation with the use of medical billing records. Method continuation and factors that were associated with early method discontinuation were evaluated with the Kaplan-Meier estimator and Cox proportional hazard models.

During the study dates, , women initiated long-acting reversible contraception. Method initiation rates remained relatively stable In analysis of women who selected intrauterine contraceptives, Among women who selected the implant, Long-acting muscarinic antagonists vs. A total of 2, studies were analyzed for possible inclusion on the basis of their title and abstract; 9 studies 17, participants were included in the analysis.

Studies utilizing the administration of GnRH in various GnRH-deficient models have revealed the critical importance of the dose and mode of delivery of this releasing factor in determining the subsequent pituitary response. Chronic administration of long acting GnRH agonists GnRHa , like continuous infusion of high doses of the native peptide, results in suppression of pituitary gonadotropin secretion.

This selective and reversible suppression of gonadotropin secretion suggested several therapeutic applications for these analogs, particularly in the treatment of central precocious puberty CPP , a disorder for which the previously available therapies lacked uniform efficacy and were associated with potential side effects.

Having selected a dose and route of administration that produced uniform suppression of spontaneous and stimulated pituitary gonadotropin secretion, GnRHa therapy resulted in a fall of gonadal sex steroid levels into the prepubertal range, a halting or regression of secondary sexual development, and a complete cessation of menses. Growth velocity slowed during therapy, with this slowing more pronounced during prolonged treatment periods and among those patients with more advanced chronological and skeletal ages.

Skeletal maturation was retarded to a greater degree than linear growth, with resultant increases in the predictions for adult stature. Moreover, these benefits have been achieved in the absence of significant side effects. Complete reversal of the suppression of gonadarche has followed discontinuation of therapy; however, patterns of growth and skeletal maturation after discontinuation of GnRHa administration remain to be characterized. Thus, the impact of GnRHa therapy on final height must await further longitudinal study.

The selective nature of GnRHa suppression of gonadarche also permits an. Long-acting reversible contraception in the pediatric emergency department: Long-acting reversible contraception LARC is recommended as first-line contraception for adolescents and young adults. As the use of LARC increases, pediatric emergency medicine clinicians should be able to recognize different types of LARC and address their common adverse effects, adverse reactions, and complications. This continuing medical education activity provides an overview of LARC and will assist clinicians in the evaluation and management of patients with LARC-associated complaints.

Hospitalizations and economic analysis in psychotic patients with paliperidone palmitate long-acting injection. Prevent hospitalizations in psychotic disorders is an important aim, so long-acting antipsychotic is a good option that can control better the correct adherence. Moreover, in the current economic context pharmacoeconomic studies are necessary.

We estimate the effect in prevention of paliperidone palmitate long-acting injection PP-LAI and calculate the economic cost in the 12 months preceding the start of treatment with PP-LAI and 12 months later. In a first analysis, we measured along one year: Background Nocturnal hypoglycemia may be the most common type of hypoglycemia in individuals with diabetes using insulin and is particularly worrisome because it often goes undetected and may lead to unconsciousness and even death in severe cases.

Objectives The prevalence, causes, and consequences of nocturnal hypoglycemia as well as detection and prevention strategies are reviewed, including the use of long-acting insulin analogs, which offer more physiologic and predictable time-action profiles than traditional human basal insulin. Results A review of these trials found that patients with type 1 and type 2 diabetes mellitus have a lower risk for nocturnal hypoglycemia when receiving long-acting insulin analogs insulin detemir or insulin glargine , provided that glycemic control is comparable to that provided by traditional human basal insulin.

Long-acting insulin analogs may be the best option to provide basal insulin coverage in patients who do not choose or require continuous subcutaneous insulin infusion. Conclusions Randomized clinical trials suggest that the long-acting insulin analogs are associated with a lower risk for nocturnal hypoglycemia than neutral protamine Hagedorn without sacrificing glycemic control. Purpose Since the adoption of highly active antiretroviral therapy, HIV disease progression has slowed across the world; however, patients are often required to take multiple medications daily of poorly bioavailable drugs via the oral route, leading to gastrointestinal irritation.

Recently, long acting antiretroviral injectables that deliver drug for months at a time have moved into late phase clinical trials. Unfortunately, these solid phase crystal formulations have inherent drawbacks in potential dose dumping and a greater likelihood for burst release of drug compared to polymeric formulations. Methods Using electrospinning, acetalated dextran scaffolds containing the protease inhibitor saquinavir were created.

Grinding techniques were then used to process these scaffolds into injectables which are termed saquinavir microconfetti. Microconfetti was analyzed for in vitro and in vivo release kinetics. Results Highly saquinavir loaded acetalated dextran electrospun fibers were able to be formed and processed into saquinavir microconfetti while other polymers such as poly lactic-co-glycolic acid and polycaprolactone were unable to do so. Saquinavir microconfetti release kinetics were able to be tuned via drug loading and polymer degradation rates.

In vivo, a single subcutaneous injection of saquinavir microconfetti released drug for greater than a week with large tissue retention. Conclusions Microconfetti is a uniquely tunable long acting injectable that would reduce the formation of adherence related HIV resistance. Our findings suggest that the injectable microconfetti delivery system could be used for long acting controlled release of saquinavir and other hydrophobic small molecule drugs. Long-acting atypical injectable antipsychotics in the treatment of schizophrenia: Although atypical antipsychotics have beneficial efficacy and tolerance, non-adherence and partial adherence remain in patients treated for schizophrenia.

Long-acting injectable or depot atypical antipsychotics offer better medication adherence and tolerability advantages. Currently, two drugs are available for the treatment of schizophrenia, risperidone long-acting injectable RLAI and olanzapine pamoate OP. RLAI and OP show good short- and long-term safety when treating patients with schizophrenia, with uncommon discontinuation due to adverse effects.

RLAI and OP data show rare problems with injection site reactions and patients exposed to injectable treatments prefer to continue injections. Healthcare providers, patients and family members should be made aware of the safety and benefits of long-acting injectable atypical antipsychotics in order to diminish the unnecessary restrictions of these therapies for patients with schizophrenia.

Possible long-acting risperidone-induced hypothermia precipitating phenytoin toxicity in an elderly patient. Thermodysregulation, including hypothermia, is recognized as a potential adverse effect secondary to atypical antipsychotics. We report the first known case of hypothermia possibly associated with long-acting risperidone depot injection, precipitating further adverse events secondary to supratherapeutic phenytoin concentrations. During the 3 months preceding admission, phenytoin dosing was stable and consecutive therapeutic concentrations were documented.

The only recent change in medication regimen was a switch from oral risperidone to the long-acting injectable formulation.

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Upon discontinuation of the risperidone and phenytoin, the patient's mental status and laboratory abnormalities returned to baseline. The patient did not experience additional seizure activity. This unintentional significant drop in core body temperature may have resulted in altered metabolism of phenytoin leading to supratherapeutic concentrations and subsequent tonic-clonic seizures, bradycardia and neutropenia. Low core body temperatures can alter the pharmacokinetic profiles of hepatically metabolized medications, prompting careful patient assessment especially in those receiving medications with a narrow-therapeutic index.

Hypothermia should be recognized as a potential adverse event with the long-acting injectable formulation of risperidone. Long-term use of short- and long-acting nitrates in stable angina pectoris. Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin NTG , a short-acting nitrate, is suitable for the immediate relief of angina.

In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance.

During long-lasting nitrate therapy, except pentaerythritol tetranitrate PETN , one can observe the development of reactive oxygen species ROS inside the muscular cell of a vessel wall, and these bind with nitric oxide NO. This leads to decreased NO activity, thus, nitrate tolerance. Making the leap from daily oral dosing to long-acting injectables: There are now long-acting versions of six antipsychotic drugs on the U.

Oily solutions of lipophilic prodrugs were the first to enter the LAIA market, but they relied on esterification of a hydroxyl handle that was lost with the emergence of the atypical antipsychotics. A review of the literature and patents shows that companies tested many different approaches before reaching the currently marketed versions, including aqueous suspensions of poorly soluble salts, polymeric microspheres, and new approaches to making prodrugs. Yet, very little has been published to support faster development of safe long-acting injectables LAIs.

This review introduces some of the critical considerations in creating an LAI; then it analyzes the existing products and discusses areas where further research is needed. The available literature suggests that lipophilic prodrugs may be inherently safer than poorly soluble salts as LAIs. Other areas needing additional study include 1 the range of physical properties acceptable for LAIs and the effect of prodrug tail length in achieving them, and 2 the role of physiological responses at the injection site in the release of drug from a depot.

In Arabidopsis flowering pathway, MADS-box genes encode transcription factors, with their structures and functions highly conserved in many species. Gh SOC1 was additionally transformed into upland cotton. Tissue-specific expression analysis of Gh SOC1 and Gh MADS42 revealed spatiotemporal expression patterns involving high transcript levels in leaves, shoot apical buds, and flowers. Overexpression of Gh SOC1 in upland cotton also produced variations in floral organs. Finally, yeast two-hybrid and bimolecular fluorescence complementation approaches were undertaken to better understand the interaction of Gh SOC1 and other MADS-box factors.

Growth hormone GH secretion and pituitary size in children with short stature. Efficacy of GH therapy in GH -deficient children, depending on the pituitary size. Certain relationships between pituitary size and growth hormone GH secretion have previously been observed, however they are still a matter of controversy. Organic abnormalities of the hypothalamic-hypophyseal region are important for predicting growth response to GH therapy.

The analysis comprised short children boys. Two GH stimulation tests, as well as magnetic resonance image MRI examination, were performed in each patient. Significant correlations were found between pituitary height and GH secretion p GH secretion were observed among the groups 6. The highest growth improvement was noticed in patients with HP for the height age.

Pituitary hypoplasia for the height age is related to more severe GH deficiency and the best response to GH therapy. Contrasting weight changes with LY, a novel long-acting insulin, and insulin glargine despite similar improved glycaemic control in T1DM and T2DM. Exploratory analyses were conducted to further characterize these findings. Pearson correlations between change in body weight and other variables were calculated. Continuous variables were analysed using a mixed linear model with repeated measurements.

Weight loss was more common in LYtreated patients than in patients treated with insulin glargine T2DM: This weight change is independent of baseline BMI or hypoglycaemia. Investigation of PEG crystallization in frozen and freeze-dried PEGylated recombinant human growth hormone-sucrose systems: The phase transitions during freeze-thawing of an aqueous solution containing PEG-rh GH and sucrose were characterized by differential scanning calorimetry.

Chemical decomposition methionine oxidation and deamidation and irreversible aggregation were characterized by size-exclusion and ion-exchange chromatography, and tryptic mapping. PEG crystallization was facilitated when it was covalently linked with rh GH. When the solutions were frozen, phase separation into PEG-rich and sucrose-rich phases facilitated PEG crystallization and the freeze-dried cake contained crystalline PEG.

Interestingly, during storage, there was no change in PEG crystallinity in formulations with medium and high PEG to sucrose ratios. Although PEG crystallization during freeze-drying did not cause protein degradation, crystallization during storage might have influenced protein stability.

Anaphylaxis to pegylated liposomal Doxorubicin: Liposomal doxorubicin is used for the treatment of various cancers like epithelial ovarian cancers, multiple myeloma and sarcomas. We report the first case of anaphylaxis to pegylated liposomal doxorubicin. Anaphylaxis to Pegylated Liposomal Doxorubicin: In this paper, Ibuprofen, a water insoluble drug was covalently attached to PEGylated nanoparticles.

Therefore, PEGylated nanoparticles contain NH2 groups over the surface of nanoparticles and can be used for the further attachment of biomolecules. The synthesis had been carried out under two different pH environments, as the solubility of Ibuprofen is pH dependent. The results strongly suggest the successful chemical conjugation of Ibuprofen to PEGylated nanoparticles in aqueous media and they could be further used for drug delivery applications.

Data were extracted for outcomes of interest, including change in trough forced expiratory volume in 1 second tFEV1 from baseline, St. Following screening, a total of 27 trials from 26 publications with 30, subjects were eligible for inclusion in the NMA. Meta-regression controlling for post-bronchodilator percentage of tFEV1 predicted at baseline as well as meta-regression adjusting for concomitant use of inhaled corticosteroids at baseline was performed to assess the magnitude of effect modification and produced similar results as observed in the base case analysis.

Cross-sectional comparison of first-generation antipsychotic long-acting injections vs risperidone long-acting injection: The current design cannot determine whether differences would have been evident earlier on during treatment. These results should be regarded as preliminary and are subject to prescribing bias. Randomized studies avoid prescribing bias and are a superior way to compare specific LAIs.

Ideally randomized studies should include patient-rated outcome measures including. Two peptides with sequence similarities to growth hormone releasing hormone GHRH have been identified by analysis of the chicken genome. One of these peptides, chicken c GHRH-LP like peptide was previously found to poorly bind to chicken pituitary membranes or to cloned and expressed chicken GHRH receptors and had little, if any, growth hormone GH -releasing activity in vivo or in vitro.